FDA Grants Priority Review to CC-486 for the Treatment of Acute Myeloid Leukemia

The FDA granted priority review to a new drug application for CC-486 for the maintenance treatment of adult patients with acute myeloid leukemia based on efficacy and safety results from the pivotal phase III QUAZAR AML-001 study.

The FDA granted priority review to a new drug application (NDA) for CC-486 for the maintenance treatment of adult patients with acute myeloid leukemia (AML) who achieved complete remission (CR) or CR with incomplete blood count recovery (CRi) following induction therapy with or without consolidation treatment, and who are not candidates for, or who choose not to proceed to, hematopoietic stem cell transplantation.1

The FDA has set a prescription drug user fee act (PDUFA) goal date of September 3, 2020.

“Often, newly diagnosed adult patients with AML achieve a complete response with induction therapy, however many patients will relapse and experience a poor outcome. Patients in remission are seeking treatment options that decrease the likelihood of relapse and extend overall survival,” Noah Berkowitz, MD, PhD, senior vice president for Global Clinical Development and Hematology at Bristol Myers Squibb. “Today’s acceptance of our submission for CC-486 represents an important step towards a potential new maintenance treatment to address an urgent medical need for AML patients and we look forward to working with the FDA during its review of CC-486.”

The NDA was based on efficacy and safety results from the pivotal phase III QUAZAR AML-001 study, which met the primary endpoint of improved overall survival for patients receiving AML maintenance treatment with CC-486, an investigational oral hypomethylating agent, versus placebo.

The primary endpoint of the study was overall survival (OS). Key secondary endpoints included relapse-free survival (RFS), safety and tolerability, healthcare resource utilization, and patient-reported outcomes per the FACIT-Fatigue Scale and EQ-5D questionnaire.

In the phase III trial, 472 patients were enrolled within 4 months of CR or CR with CRi.2 Trial participants were randomized to receive either daily CC-486 (n = 238) or placebo (n = 234), plus best supportive care. Moreover, CC-486 was administered at 300 mg daily for 14 days followed by 14 days off therapy. However, if a CR/CRi was not maintained, the CC-486 dose could be escalated to 21 days on CC-486 with 7 days off therapy. Patients remained on treatment until unacceptable toxicity or disease progression.

In patients receiving CC-486, the best responses to prior therapy included CR for 79% of patients and CRi for 21%. In the placebo arm, the best responses were found to be CR for 84% of patients and CRi for 16%. Overall, approximately one-fifth of patients had not previously received consolidation therapy and approximately half of patients tested negative for minimal residual disease.

After a median follow-up of 41.2 months, the median OS with CC-486 was 24.7 months (95% CI, 18.7-30.5) compared with 14.8 months for placebo (95% CI, 11.7-17.6), which represented a 31% reduction in the risk of death with CC-486 (HR, 0.69; 95% CI, 0.55-0.86; P = .0009). Further, the median relapse-free survival (RFS) was 4.8 months with placebo compared with 10.3 months for CC-486 (HR, 0.65; 95% CI, 0.52-0.81; P = .0001).

At 1 year, 47% of patients were free of relapse in the CC-486 arm compared with 29% in the placebo group. Notably, the benefits in both RFS and OS were seen across key prognostic AML subgroups.

The safety profile for CC-486 was consistent with injectable azacitidine (Vidaza), with infrequent treatment discontinuation related to adverse events (AEs). Additionally, there were no treatment-related deaths. The most common all-grade AEs with CC-486 included nausea (65%), vomiting (60%), diarrhea (50%), and constipation (39%). The most common grade 3 or 4 AEs in both treatments groups were neutropenia (41% vs 24%), thrombocytopenia (23% vs 22%), anemia (14% vs 13%), diarrhea (5% vs 1%), vomiting (3% vs 0%), fatigue (3% vs 1%), and nausea (3% vs 0.4%), respectively.

CC-486 is not currently approved for use in any country.


1. U.S. Food and Drug Administration (FDA) Accepts for Priority Review Bristol Myers Squibb’s Application for CC-486 for Maintenance Treatment of Adult Patients in Remission with Acute Myeloid Leukemia [news release]. Princeton, NJ. Published May 1, 2020. news.bms.com/press-release/corporatefinancial-news/us-food-and-drug-administration-fda-accepts-priority-review-br. Accessed May 1, 2020.

2. Wei AH, Dӧhner H, Pocock C, et al. The QUAZAR AML-001 Maintenance Trial: Results of a Phase III International, Randomized, Double-Blind, Placebo-Controlled Study of CC-486 in Patients with Acute Myeloid Leukemia (AML) in First Remission. Presented at: 2019 ASH Annual Meeting, Orlando, FL, December 7-10, 2019. Abstract LBA3.